Self-folded silyl cavitands with In- and outwardly directed allyl groups

Article abstract of DOI:10.1002/ejoc.201301843

Cavitands endowed with in- and outwardly directed allylsilanes are described; epoxidation reactions of the allyl groups with meta-chloroperbenzoic acid are included. The synthesis of introverted and extroverted allylsilanes tethered to triquinoxaline-spanned resorcinarenes was successfully achieved. Competitive epoxidation experiments between the two isomers disclosed that the introverted allyl was more reactive than the extroverted allyl, despite a clearly congested nuisance: the vase-formed cavity would actively stabilize the reaction process. Copyright

Full text of DOI:10.1002/ejoc.201301843

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201301843
Self-Folded Silyl Cavitands with In- and Outwardly Directed Allyl Groups
Kazuhiro Ohashi,[a] Kouhei Ito,[a] and Tetsuo Iwasawa*[a]
Keywords: Supramolecular chemistry / Cavitands / Macrocycles / Silanes / Introverted functionality
Cavitands endowed with in- and outwardly directed allyl-
silanes are described; epoxidation reactions of the allyl
groups with meta-chloroperbenzoic acid are included. The
synthesis of introverted and extroverted allylsilanes tethered
to triquinoxaline-spanned resorcinarenes was successfully
achieved. Competitive epoxidation experiments between the
two isomers disclosed that the introverted allyl was more re-
active than the extroverted allyl, despite a clearly congested
nuisance: the vase-formed cavity would actively stabilize the
reaction process.
ality can recognize guests,[8] accelerate[9] and catalyze reac-
tions,[10] and stabilize reactive intermediates.[11,12] Despite
Introduction
Natural supramolecular systems integrate inwardly directed the relevant role played by inwardly functionalized cavit-
functions. The binding sites of enzymes, poly-
peptides, and RNA strands can fold around a substrate, and
in the folded state the functionality converges on the sub-
strate.[1,2] The introverted functionalities in biological
macromolecules play quintessential roles in catalysis.[3]
In a similar vein, a synthetic approach to the chemical
space with introverted functionality has been pioneered,[4–6]
particularly by Rebek and co-workers.[7] They use the
deepened cavitand derived from Högberg’s resorcinarene
scaffold and four aromatic exteriors. The functional sub-
stituent is up in the interior space, like a fishing line, toward
the tapered end. Indeed, there are many parallels between
the synthetic and natural systems: the introverted function-
Scheme 1. Triquinoxaline-spanned resorcin[4]arene 1.
Scheme 2. Synthesis of cavitands 2 and 3.
[a] Department of Materials Chemistry, Faculty of Science and
Technology, Ryukoku University,
ands in supramolecular chemistry, the organization of reac-
tion sites inside the space is underrepresented owing to the
synthetic difficulty in functionalizing concave surfaces.[13]
To overcome this intrinsic problem would expand the pos-
sibilities and importance of functionalized cavitands.
Seta, Otsu 520-2194, Japan
E-mail: iwasawa@rins.ryukoku.ac.jp
http://www.chem.ryukoku.ac.jp/iwasawa/index.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301843.
Eur. J. Org. Chem. 2014, 1597–1601
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1597

K. Ohashi, K. Ito, T. Iwasawa
SHORT COMMUNICATION
Herein, we report a novel synthesis of self-folded silyl
On the basis of the results in Figure 1, the difference in
cavitands endowed with in- and outwardly directed allyl the chemical shifts (Δδ values) between 2 and 3 are summa-
groups. The reactions of triquinoxaline-spanned cavitand 1 rized in Figure 2. The protons of the CH2 and CH3 groups
(Scheme 1) with allyl(dichloro)methylsilane yielded isomers directly bonded to the silicon atoms show relatively large
of introverted allyl 2 and extroverted allyl 3 (Scheme 2). values of approximately 1.7. This suggests that the closest
Analysis by NMR spectroscopy elucidated that the cavity position to the silicon atom is most sufficiently covered by
of 2 definitely holds an allyl moiety; functionalizing the the anisotropic effect of the strong π surrounding endued
concave surfaces was successfully achieved. In addition, the with the inner space. Interestingly, the Hd and He protons
two isomers underwent epoxidation with meta-chloroper- in the exo methylene unit showed quite different Δδ values:
benzoic acid (mCPBA), and 2 was more reactive than 3 in Δδ = 0.37 for Hd is the smallest, and Δδ = 0.85 for He is
competitive experiments.
comparable with the value for Hc. This implies that in 2,
the Hd proton is outside the strong magnetically shielded
environment, and this directs He to the concave portion of
the shaped surface.
Results and Discussion
We commenced the reaction of 1 with commercially
available allyl(dichloro)methylsilane. The reactions pro-
ceeded smoothly in 2 h in toluene with complete consump-
tion of 1 (Scheme 2). An isomeric mixture of 2 and 3 was
obtained; the separation of 2 from 3 was a terribly pesky
operation, because these compounds had nearly the same
Rf values in several eluents. Employment of a large amount
of silica gel gave separate fractions of single isomers of each
2 and 3 in 34 and 27% yield, respectively. As each ratio of
2/3 in the crude state was nearly comparable to 1:1, selective
substitution reactions of the allyl(dichloro)methylsilane
with 1 did not occur.
Figure 2. The differences in the chemical shifts (Δδ) in [D8]toluene
between the in- and outwardly directed allyl protons of 2 and 3.
The values are standardized as (δ of 2) – (δ of 3).
Scheme 3 illustrates epoxidation reactions of 2 and 3
(1 equiv.) with mCPBA (1 equiv.) in toluene. Almost all of
the starting allyl compounds disappeared, as indicated by
TLC monitoring, and both compounds underwent clean
transformations. However, purification by column
chromatography seemed to decrease the yield to 54% for 4
and to 46% for 5. As depicted in Figure 3, the mid- and
upfield portions of the 1H NMR spectra of 4 and 5 in [D8]-
toluene show characteristic signatures of epoxide moieties
with reasonable Δδ values. Specifically, the geminal protons
of SiCH2 for 4 are located at δ = –0.60 ppm with J = 15.4
and 7.0 Hz and at δ = –0.8 ppm with J = 15.4 and 5.4 Hz.
1
Portions of the H NMR spectra of 2 and 3 in [D8]tolu-
ene are shown in Figure 1. The CH methine protons, which
are located directly below the quinoxaline units, are situated
in the mid-field region at δ = 6.14, 6.05, and 4.77 ppm.
These values indicate that the vase conformation was en-
sured.[4c,14,15] It is possible to distinguish between 2 and 3,
because the magnetically shielded environment caused by
the inner space shifts inwardly directed protons strongly up-
field.[16] The upfield portions near δ = 0 ppm shows two
sets of signals: Ha/Hb at δ = 0.28/–0.13 ppm and Ha/Hb at
δ = –1.32/1.66 ppm. This indicates that Hb in the former
and Ha in the latter are enclosed by the space: thus, the
orientation of the substituents on the silicon atom was de-
termined.
Figure 1. Mid- and upfield portions of the 1H NMR spectra for
(a) 2 and (b) 3 (400 MHz, [D8]toluene). The resonance labelled with
“ϫ” corresponds to water.
Scheme 3. Epoxidation of allylsilanes 2 and 3.
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Self-Folded Silyl Cavitands
der the oxidation process; that is, the magnetic environment
inside the cavity promotes the reaction. This is supported
by the result of entry 4 in Table 1: no epoxidation proceeded
in [D12]mesitylene, and 2 and 3 remained untouched.[18]
[D12]Mesitylene is larger in size than [D10]-p-xylene, [D8]-
toluene, and [D6]benzene, and thus it cannot fit inside the
1
cavity; in fact, the signals in the H NMR spectra of 2 and
3 in [D12]mesitylene are too broad to assign.[19] The quinox-
aline substructures in mesitylene are not arranged in a fixed
order to equilibrate between the vase and kite form, and
consequently, the floating quinoxalines sterically hinder
each allyl group in 2 and 3 and stop the epoxidation.
Table 2. A competitive epoxidation reaction between 2 and 6.[a,b]
Figure 3. Upfield portion of the 1H NMR spectra for (a) 4 and (b)
5 (400 MHz,[D8]toluene).
With a workable protocol in hand, competitive reactions
between 2 and 3 were evaluated through clean epoxidation
(Table 1). The experiments in NMR tubes were performed
in [D6]benzene, [D8]toluene, [D10]-p-xylene, and [D12]-
mesitylene,[15] and ratios of 4/5/2/3 are summarized. The ra-
tios of 4/5 are around 30:20 through entries 1–3, and they
are consistent with the conversions of 2 and 3: in brief, 4
significantly exceeds 5 in yield.[17] The reaction center of the
allyl group in 2 is located at a more congested area than in
3 because the quinoxaline encapsulates the allyl, and there-
fore, smooth epoxidation should occur for 3 but not for 2.
In reality, better reactivity was observed for 2, contrary to
our expectation.
Yield [%][c]
4
7
2
6
26
24
25
25
[a] Conditions: 2 (0.02 mmol, 31 mg), 6 (0.02 mmol, 6 mg), and
mCPBA (0.02 mmol, 5 mg) in [D8]toluene (0.5 mL) in an NMR
tube. [b] All of the starting mCPBA (1 equiv.) was consumed.
1
[c] Determined by H NMR spectroscopy.
How does the vase-shaped cavity enhance the reactivity
beyond steric hindrance? Its dense π-orbital space could de-
localize electrons that interchange between the allyl group
and mCPBA during the course of the reaction. Thus, the
cavity stabilizes the process and reduces the enthalpic price
of the reaction. The reactants are confined in a limited
space and are properly placed, and the desired reactive spe-
cies would be actively stabilized.[20]
Table 1. Competitive epoxidation reactions between 2 and 3.[a,b]
Entry
Solvent
Yield [%][c]
4
5
2
3
1
2
[D6]benzene
[D8]toluene
27
32
17
23
24
19
32
26
3
[D10]-p-xylene
[D12]mesitylene
31
18
19
≈50
32
≈50
4[d]
≈0[e]
≈0[e]
Conclusions
[a] Conditions: 2 (0.02 mmol, 31 mg), 3 (0.02 mmol, 31 mg), and
mCPBA (0.02 mmol, 5 mg) with the deuterated solvent (0.5 mL) in
an NMR tube. [b] All of the starting mCPBA (1 equiv.) was con-
sumed. [c] Determined by 1H NMR spectroscopy. [d] Many signals
were too broad to assign: C9D12 does not fit for each cavity of 2
and 3. [e] No reaction was observed by TLC analysis, and starting
2 and 3 remained.
In summary, we have successfully inserted a reactive allyl
group inside cavitand 1, and its magnetic environment in-
side the capsule proved to be unusual because of the many
aromatic rings that enclose it. The NMR signals of the en-
capsulated allyl are thus profoundly altered relative to those
of the outward allyl, and so it is easily distinguished from its
Given the observed reactivity of 2, we worked on com- unrestrained counterparts. The introverted allyl underwent
petitive reactions between 2 and 6 (Table 2). Compound 6 mCPBA-mediated epoxidation and unexpectedly showed
was derived from p-cresol, and it is sterically unhindered higher reactivity than the extroverted allyl. Through exami-
relative to 2. Less-congested 6 should undergo faster epox- nation in [D12]mesitylene and a competitive experiment
idation than 4 to afford 7; however, surprisingly, the ratio with small allyl 6, a remarkably salient feature was revealed
of 7/4 was nearly the same: 26:24. The competition proved in the vase form, which is capable of holding the reactive
that the reactivity of encumbered allyl 2 was comparable to allyl moiety. Further synthetic development of function-
that of unfortified allyl 6. The results in Tables 1 and 2 sug- alized cavitands is ongoing and will be reported in due
gest that well-arrayed quinoxalines of 2 do not merely hin- course.
Eur. J. Org. Chem. 2014, 1597–1601
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1599

K. Ohashi, K. Ito, T. Iwasawa
SHORT COMMUNICATION
1153 cm–1. C100H124N6O8Si (1566.20): calcd. C 76.69, H 7.98, N
5.37; found C 76.32, H 7.96, N 5.02.
Experimental Section
Synthesis of Cavitand 2 and 3: Under an argon atmosphere, a two-
necked flask was charged with 1 (1 mmol, 1.48 g), triethylamine
(2.4 mmol, 0.33 mL), and anhydrous toluene (20 mL). Allyl(di-
chloro)methylsilane (1.1 mmol, 0.16 mL) was then added. After
stirring at ambient temperature for 2 h, the reaction mixture was
filtered through a pad of cotton and concentrated in vacuo to give
the crude products as white solid materials. Purification by silica gel
column chromatography (hexane/ethyl acetate 9:1) yielded target 2
(533 mg, 34%) as a white solid material and 3 (417 mg, 27%) as a
white solid material. Data for 2: Yield 34% (533 mg), white solid.
1H NMR (400 MHz, CDCl3): δ = 8.28 (s, 2 H), 7.92–7.84 (m, 4
H), 7.67 (d, J = 8.2 Hz, 2 H), 7.55–7.44 (m, 6 H), 7.33 (s, 2 H),
7.18 (s, 2 H), 7.16 (s, 2 H), 5.76 (t, J = 8.1 Hz, 1 H), 5.68 (t, J =
Supporting Information (see footnote on the first page of this arti-
cle): General procedures and characterization data of new com-
pounds.
Acknowledgments
The authors are pleased to thank Dr. Fukashi Matsumoto at
OMTRI for assistance with MALDI-MS. Professor Michael P.
Schramm at CSULB is thanked for helpful discussions.
[1] a) J. A. Gerlt, Chem. Rev. 1987, 87, 1079–1105; b) J. C. M.
van Hest, D. A. Tirrel, Chem. Commun. 2001, 1897–1904; c)
M. V. Rodnina, W. Wintermeyer, Curr. Opin. Struct. Biol. 2003,
13, 334–340; d) K. Shen, A. C. Hines, D. Schwarzer, K. A.
Pickin, P. A. Cole, Biochim. Biophys. Acta Proteins Proteomics
2005, 1754, 65–78.
[2] a) G. Varani, Annu. Rev. Biophys. Biomol. Struct. 1995, 24,
379–404; b) V. J. DeRose, Curr. Opin. Struct. Biol. 2003, 13,
317–324; c) S. Shuman, C. D. Lima, Curr. Opin. Struct. Biol.
2004, 14, 757–764.
[3] a) A. J. Skerra, J. Mol. Recognit. 2000, 13, 167–187; b) G. Folk-
ers, C. D. P. Klein, Angew. Chem. Int. Ed. 2001, 40, 4175–4177;
Angew. Chem. 2001, 113, 4303–4305; c) C. Khosla, P. B. Har-
bury, Nature 2001, 409, 247–252; d) T. C. Bruice, Acc. Chem.
Res. 2002, 35, 139–148.
[4] a) J. R. Moran, S. Karbach, D. J. Cram, J. Am. Chem. Soc.
1982, 104, 5826–5828; b) D. J. Cram, Science 1983, 219, 1177–
1183; c) J. R. Moran, J. L. Ericson, E. Dalcanale, J. A. Bryant,
C. B. Knobler, D. J. Cram, J. Am. Chem. Soc. 1991, 113, 5707–
5714; d) D. J. Cram, J. M. Cram, Container Molecules and
Their Guests, Royal Society of Chemistry, Cambridge, 1994, p.
85–130.
[5] a) P. Timmerman, M. G. A. van Mook, W. Verboom, G. J.
van Hummel, S. Harkema, D. N. Reinhoudt, Tetrahedron Lett.
1992, 33, 3377–3380; b) P. Timmerman, H. Boerrigter, W. Ver-
boom, G. J. van Hummel, S. Harkema, D. N. Reinhoudt, J. In-
clusion Phenom. Mol. Recognit. Chem. 1994, 19, 167–191; c) P.
Timmerman, W. Verboom, D. N. Reinhoudt, Tetrahedron 1996,
52, 2663–2704; d) H. Boerrigter, W. Verboom, G. J. van Hum-
mel, S. Harkema, D. N. Reinhoudt, Tetrahedron Lett. 1996, 37,
5167–5170.
[6] a) T. N. Sorrell, F. C. J. Pigge, Org. Chem. 1993, 58, 784–785;
b) T. Haino, T. Harano, K. Matsumura, Y. Fukazawa, Tetrahe-
dron Lett. 1995, 36, 5793–5796; c) T. Haino, K. Matsumura, T.
Harano, K. Yamada, Y. Saijyo, Y. Fukazawa, Tetrahedron
1998, 54, 12185–12196; d) J. L. Irwin, M. S. Sherbum, J. Org.
Chem. 2000, 65, 602–605; e) T. Haino, M. Kobayashi, M. Chi-
karaishi, Y. Fukazawa, Chem. Commun. 2005, 18, 2321–2323.
[7] a) D. M. Rudkevich, J. Rebek Jr., Eur. J. Org. Chem. 1999,
1991–2005; b) T. Haino, D. M. Rudkevich, A. Shivanyuk, K.
Rissanen, J. Rebek Jr., Chem. Eur. J. 2000, 6, 3797–3805; c)
B. W. Purse, J. Rebek Jr., Proc. Natl. Acad. Sci. USA 2005, 102,
10777–10782.
8.0 Hz,
2 H), 5.41 (ddt, J = 17.1, 10.1, 8.0 Hz, 1 H,
SiCH2CH=CH2), 4.82 (d, J = 10.1 Hz, 1 H, SiCH2CH=CH2), 4.62
(d, J = 17.1 Hz, 1 H, SiCH2CH=CH2), 4.54 (t, J = 7.9 Hz, 1 H),
2.34–2.19 (m, 8 H), 1.47–1.29 (m, 72 H), 0.96–0.85 (m, 12 H), 0.81
(d, J = 8.0 Hz, 2 H, SiCH2CH=CH2), 0.47 (s, 3 H, SiCH3) ppm.
1H NMR (400 MHz, [D8]toluene): δ = 8.71 (s, 2 H), 8.00 (d, J =
8.2 Hz, 2 H), 7.76 (s, 2 H), 7.67 (d, J = 8.2 Hz, 2 H), 7.63 (s, 2 H),
7.54 (dd, J = 6.3, 3.4 Hz, 2 H), 7.47 (s, 2 H), 7.24 (dd, J = 8.2,
8.2 Hz, 2 H), 7.12–7.04 (m, 4 H), 6.16 (t, J = 8.2 Hz, 2 H), 6.05 (t,
J = 8.2 Hz, 1 H), 4.94 (ddt, J = 17.0, 10.5, 8.0 Hz, 1 H,
SiCH2CH=CH2), 4.74 (t, J = 8.0 Hz, 1 H), 4.58 (dd, J = 10.5,
2.0 Hz, 1 H, SiCH2CH=CH2), 4.10 (dd, J = 17.0, 2.0 Hz, 1 H,
SiCH2CH=CH2), 2.50–2.32 (m, 8 H), 1.57–1.29 (m, 72 H), 0.96–
0.93 (m, 12 H), 0.28 (s, 3 H, SiCH3), –0.13 (d, J = 8.0 Hz, 2 H,
SiCH2CH=CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.3,
153.1, 153.0, 152.9, 152.7, 152.6, 150.3, 140.2, 140.08, 140.06,
136.9, 136.3, 134.6, 133.0, 131.6, 129.7, 129.6, 129.4, 128.15,
128.11, 127.9, 124.2, 123.0, 119.0, 116.1, 115.8, 35.4, 34.5, 34.3,
32.9, 32.7, 32.3 (many peaks are overlapped), 30.1 (many peaks are
overlapped), 29.8 (many peaks are overlapped), 28.4, 23.1 (many
peaks are overlapped), 19.7, 14.5 (many peaks are overlapped),
–4.7 ppm. MS (FAB): m/z = 1567 [M+H]+. IR (neat): ν = 2921,
˜
2850, 1482, 1414, 1331, 1158 cm–1. C100H124N6O8Si (1566.20):
calcd. C 76.69, H 7.98, N 5.37; found C 76.79, H 7.90, N 5.01.
1
Data for 3: Yield 27% (417 mg), white solid. H NMR (400 MHz,
CDCl3): δ = 8.26 (s, 2 H), 7.90–7.85 (m, 4 H), 7.66 (d, J = 8.2 Hz,
2 H), 7.55–7.43 (m, 6 H), 7.30 (s, 2 H), 7.14 (s, 2 H), 7.12 (s, 2 H),
5.94 (ddt, J = 17.0, 10.1, 7.8 Hz, 1 H, SiCH2CH=CH2), 5.73 (t, J
= 8.0 Hz, 1 H), 5.65 (t, J = 8.1 Hz, 2 H), 5.11 (d, J = 17.0 Hz, 1
H, SiCH2CH=CH2), 5.06 (d, J = 10.1 Hz, 1 H, SiCH2CH=CH2),
4.55 (t, J = 7.8 Hz, 1 H), 2.35–2.19 (m, 8 H), 1.94 (d, J = 7.8 Hz,
2 H, SiCH2CH=CH2), 1.45–1.29 (m, 72 H), 0.94–0.84 (m, 12 H),
1
–0.56 (s, 3 H, SiCH3) ppm. H NMR (400 MHz, [D8]toluene): δ =
8.69 (s, 2 H), 7.97 (d, J = 8.0 Hz, 2 H), 7.73 (s, 2 H), 7.61–7.56 (m,
6 H), 7.43 (s, 2 H), 7.24 (dd, J = 7.2, 7.2 Hz, 2 H), 7.09–7.06 (m,
4 H), 6.14 (t, J = 8.1 Hz, 2 H), 6.05 (t, J = 8.1 Hz, 1 H), 5.81
(ddt, J = 17.5, 9.4, 7.8 Hz, 1 H, SiCH2CH=CH2), 4.95 (m, 2 H,
SiCH2CH=CH2, two peaks are overlapped), 4.77 (t, J = 7.9 Hz, 1
H), 2.47–2.34 (m, 8 H), 1.66 (d, J = 7.8 Hz, 2 H, SiCH2CH=CH2),
1.48–1.29 (m, 72 H), 0.99–0.89 (m, 12 H), –1.32 (s, 3 H, SiCH3)
ppm. 13C NMR (100 MHz, CDCl3): δ = 153.3, 153.2, 153.0, 152.9,
152.7, 152.6, 150.4, 140.13, 140.11, 140.05, 136.9, 136.3, 134.7,
132.9, 131.8, 129.6, 129.5, 129.3, 128.2, 128.1, 127.9, 124.2, 123.0,
118.9, 116.2, 116.0, 35.2, 34.6, 34.3, 32.8, 32.7, 32.3 (many peaks
are overlapped), 30.1 (many peaks are overlapped), 29.8 (many
peaks are overlapped), 28.4, 23.1 (many peaks are overlapped),
21.7, 14.5 (many peaks are overlapped), –6.2 ppm. MS (FAB): m/z
[8] A. R. Renslo, J. Rebek Jr., Angew. Chem. Int. Ed. 2000, 39,
3281–3283; Angew. Chem. 2000, 112, 3419–3421.
[9] B. W. Purse, P. Ballester, J. Rebek Jr., J. Am. Chem. Soc. 2003,
125, 14682–14683.
[10] A. Gissot, J. Rebek Jr., J. Am. Chem. Soc. 2004, 126, 7424–
7425.
[11] a) T. Iwasawa, R. J. Hooley, J. Rebek Jr., Science 2007, 317,
493–496; b) T. Iwasawa, P. L. Wash, C. Gibson, J. Rebek Jr.,
Tetrahedron 2007, 63, 6506–6511; c) R. J. Hooley, T. Iwasawa,
J. Rebek Jr., J. Am. Chem. Soc. 2007, 129, 15330–15339; d) R. J.
Hooley, P. Restorp, T. Iwasawa, J. Rebek Jr., J. Am. Chem. Soc.
2007, 129, 15639–15643.
= 1567 [M+H]+. IR (neat): ν = 2120, 2850, 1481, 1404, 1331,
˜
1600
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Self-Folded Silyl Cavitands
[12] a) S. M. Butterfield, J. Rebek Jr., J. Am. Chem. Soc. 2006, 128,
15366–15367; b) P. L. Wash, A. R. Renslo, J. Rebek Jr., Angew.
Chem. Int. Ed. 2001, 40, 1221–1222; Angew. Chem. 2001, 113,
1261–1262.
[13] a) B. Benmerad, P. Clair, D. Armspach, D. Matt, F. Baleg-
roune, L. Toupet, Chem. Commun. 2006, 2678–2680; b) K.
Goto, M. Holler, R. Okazaki, J. Am. Chem. Soc. 1997, 119,
1460–1461; c) S. Watanabe, K. Goto, T. Kawashima, R. Oka-
zaki, Tetrahedron Lett. 1995, 36, 7677–7680; d) T. K. Park, J.
Schroeder, J. Rebek Jr., J. Am. Chem. Soc. 1991, 113, 5125–
5127.
class of quinoxaline-spanned cavitands was strongly apt to
form the vase in aromatic solvents, see: A. V. Azov, B. Jaun, F.
Diederich, Helv. Chim. Acta 2004, 87, 449–462.
[16] T. Iwasawa, Y. Nishimoto, K. Hama, T. Kamei, M. Nishiuchi,
Y. Kawamura, Tetrahedron Lett. 2008, 49, 4758–4762.
[17] Differences in reaction rates between these solvents were not
particularly observed.
[18] Smooth epoxidation of allyl 6 in [D12]mesitylene was ensured.
[19] a) T. Heinz, D. Rudkevich, J. Rebek Jr., Nature 1998, 394, 764–
766; b) T. Heinz, D. Rudkevich, J. Rebek Jr., Angew. Chem. Int.
Ed. 1999, 38, 1136–1139; Angew. Chem. 1999, 111, 1206–1209.
[20] A. Fersht, Enzyme Structure and Mechanism, Freeman, New
York, 1984, p. 47–97.
[14] P. P. Castro, G. Zhao, G. A. Masangkay, C. Hernandez, L. M.
Gutierrez-Tunstad, Org. Lett. 2004, 6, 333–336.
[15] This observation is in agreement with the vase–kite switching
systems, as studied by Diederich and co-workers, in which a
Received: December 11, 2013
Published Online: February 6, 2014
Eur. J. Org. Chem. 2014, 1597–1601
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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